Glycerolipids are essential for various hepatic functions including: the formation of very low density lipoprotein; proliferation and repair of intracellular membranes; and the formation of biliary phospholipids. Elucidation of the factors which regulate glycerolipid biosynthesis may be of fundamental importance in understanding the pathogenesis of liver disease and toxin induced liver cell injury. These studies will attempt to determine if the toxic effects of various agents (ethanol, CCl4, hydrazine, morphine and bromobenzene) on the liver are related to the alterations they cause in hepatic glycerolipid biosynthesis. Many drug related liver injuries are associated with the production of reactive metabolites generated by the liver's microsomal mixed function oxidase system. Microsomes are also the primary cellular site of hepatic glycerolipid biosynthesis. Hence, reactive metabolites generated by the mixed function oxidase system may interact (bind) with the endoplasmic reticulum and initiate membrane injury. Presumably, the cell would attempt to repair injured membranes by generating new structural components (gylcerophospholipids - phosphatidyl choline and phosphatidyl ethanolamine). Therefore, we will attempt to correlate structural changes in the endoplasmic reticulum determined by electron microscopy with alterations in the enzymatic rate of hepatic glycerolipid formation utilizing whole animals, isolated hepatocytes, hepatocyte monolayers and subcellular fractions.